Fatty acid synthase (FAS or FASN) is an enzyme that catalyzes the synthesis of fatty acids. Its primary function is the de novo synthesis of palmitate from acetyl coenzyme A (acetyl-CoA) and malonyl coenzyme A (malonyl-CoA). In most normal human cells, FAS may be minimally expressed. However, in some cancers (e.g., breast cancer, prostate cancer, and lung cancer), FAS may be upregulated, and this overexpression may be associated with poor prognosis. The upregulation of FAS in cancer cells makes FAS a desirable target for chemotherapeutic inhibition and cancer therapy.
Cerulenin (IUPAC name: (2R,3S)-3-[(4E,7E)-nona-4,7-dienoyl]oxirane-2-carboxamide) was identified as a naturally occurring FAS inhibitor. However, cerulenin is chemically unstable, and its use as a therapeutic is generally limited because of this instability. ORLISTAT® (tetrahydrolipstatin; IUPAC name: (S)-((S)-1-((2S,3S)-3-Hexyl-4-oxooxetan-2-yl)tridecan-2-yl) 2-formamido-4-methylpentanoate), Hoffman-La Roche, N.J.), is used in the treatment of obesity. However, ORLISTAT® has not been extensively studied as a cancer chemotherapeutic, and ORLISTAT® may also possess cellular off-targets which may make it undesirable as a cancer chemotherapeutic. Other FAS inhibitors include triclosan, osthole, C75 (4-methylene-2-octyl-5-oxotetra-hydrofuran-3-carboxylic acid), and epigallocatechin-3-gallate (EGCG).
There is a need to identify and study novel FAS inhibitors.